The in vitro cultivation of hepatitis A virus (HAV) eluded all attempts for several decades. The modern era of advances in understanding HAV, which led eventually to in vitro cultivation of the virus, was initiated by the successful transmission of HAV to marmosets Deinhardt et al., J. Exp. Med. 125, 673 (1967), Mascoli et al Proc. Soc. Exp. Biol. Med. 142, 276 (1973) and Provost et al., Proc. Soc. Exp. Biol. Med. 142, 1257, (1973)!, by the characterization of HAV from marmoset serum and liver Provost et al., Proc. Soc. Exp. Biol. Med. 148, 532 (1975)!, and by the detection of HAV in the stools of infected humans by immune electron microscopy (IEM), Feinstone et al., Science 182, 1026 (1973)!.
Progress in cultivating and characterizing the CR 326 strain of HAV in marmosets led to its definition as a picornavirus Provost et al., Proc. Soc. Exp. Biol. Med. 148, 532 (1975)!, to the development of serologic assays for HAV antigert and antibody Provost et al., Proc. Soc. Exp. Biol. Med. 148, 962 (1975) and Miller et al., Proc. Soc. Exp. Biol. Med. 149, 254 (1975), and to the development of potent preparations of HAV from infected liver of marmosets Provost al., Proc. Soc. Exp. Biol. Med. 148, 532 (1975), and Provost et al., Proc. Soc. Exp. Biol. Med. 155, 283 (1977)!. Such preparations contained about 10.sup.9 fifty percent marmoset infectious doses per gram of liver tissue. These findings provided the background for the successful propagation of HAV in cell culture first reported by Provost et al., Proc. Soc. Exp. Biol. Med. 160, 213 (1979).
A disadvantage of the foregoing methods is that they require the use of primates that are not only expensive but in short supply and difficult to obtain. An in vitro cell culture system which did not require virus passage in vivo in a subhuman primate would be a significant advance in this art.